With an estimated 425 million diabetes patients worldwide in 2019, type 2 diabetes has reached a pandemic proportion and represents a major unmet medical need. A key determinant of the development and progression of type 2 diabetes is pancreatic ‐cell dysfunction, including the loss of cell mass, the impairment of insulin biosynthesis and inadequate exocytosis. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), a Ca²⁺‐permeable non‐selective cation channel, is involved in ‐cell replication, insulin production and secretion. TRPV4 agonists have insulinotropic activity in pancreatic ‐cell lines, but the prolonged activation of TRPV4 leads to ‐cell dysfunction and death. In addition, TRPV4 is involved in a wide variety of pathophysiological activities, and has been reported to play an important role in diabetes‐related complications, such as obesity, cardiovascular diseases, diabetic retinopathy, nephropathy and neuropathy. In a rodent type 2 diabetes model, Trpv4 agonists promote vasodilation and improve cardiovascular function, whereas Trpv4 antagonists reduce high‐fat diet‐induced obesity, insulin resistance, diabetic nephropathy, retinopathy and neuropathy. These findings raise interest in using TRPV4 as a therapeutic target for type 2 diabetes. In this review, we intend to summarize the latest findings regarding the role of TRPV4 in diabetes as well as diabetes‐related conditions, and to evaluate its potential as a therapeutic target for diabetes and diabetes‐related diseases.

中文翻译：

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瞬时受体潜在香草酸 4 通道作为糖尿病和糖尿病相关并发症的治疗靶点。

2019 年，全球估计有 4.25 亿糖尿病患者，2 型糖尿病已达到流行病的比例，是一个未得到满足的重大医疗需求。2 型糖尿病发生和进展的一个关键决定因素是胰腺细胞功能障碍，包括细胞质量损失、胰岛素生物合成受损和胞吐作用不足。最近的研究表明，瞬时受体电位香草酸 4 (TRPV4) 是一种 Ca ²⁺渗透性非选择性阳离子通道，参与细胞复制、胰岛素产生和分泌。TRPV4 激动剂在胰腺细胞系中具有促胰岛素活性，但 TRPV4 的长期激活会导致细胞功能障碍和死亡。此外，TRPV4还参与多种病理生理活动，据报道在肥胖、心血管疾病、糖尿病视网膜病变、肾病和神经病变等糖尿病相关并发症中发挥重要作用。在啮齿类 2 型糖尿病模型中，Trpv4 激动剂可促进血管舒张并改善心血管功能，而 Trpv4 拮抗剂可减少高脂饮食引起的肥胖、胰岛素抵抗、糖尿病肾病、视网膜病变和神经病变。这些发现引起了人们对使用 TRPV4 作为 2 型糖尿病治疗靶点的兴趣。在这篇综述中，我们打算总结有关TRPV4在糖尿病以及糖尿病相关疾病中的作用的最新发现，并评估其作为糖尿病和糖尿病相关疾病的治疗靶点的潜力。